Effect of the effluent released from the canine internal mammary artery after intraluminal and extraluminal perfusion of acetylcholine and adenosine diphosphate

Segments of the canine internal mammary artery (35 mm in length) were suspended in vitro in an organ chamber containing physiological salt solution (95% O2/5% CO2, pH = 7.4, 37°C). Segments were individually cannulated and perfused at 5 ml/minute using a roller pump. Vasorelaxant activity of the effluent from the perfused internal mammary arteries was bioassayed by measuring the decrease in tension induced by the effluent of the coronary artery endothelium-free ring which had been contracted with prostaglandin F2α (2 × 10-6 M). Intraluminal perfusion of adenosine diphosphate (10-5 M) induced significant increase in relaxant activity in the effluent from the perfused blood vessel. However, when adenosine diphosphate (10-5 M) was added extraluminally to the internal mammary artery, no change in relaxant activity in the effluent was noted. In contrast, acetylcholine produced significant increase in the relaxant activity on the effluent of the perfused internal mammary artery with both intraluminal and extraluminal perfusion. The intraluminal and extraluminal release of endothelium-derived relaxing factor (EDRF) by acetylcholine (10-5 M) can be inhibited by site-specific administration of atropine (10-5 M). These experiments indicate that certain agonists can induce the release of EDRF only by binding to intravascular receptors while other agonists can induce endothelium-dependent vasodilatation by acting on neural side receptors

High-frequency ultrasonic waves cause endothelial dysfunction on canine epicardial coronary arteries

OBJETIVO: Aplicação de energia por ultra-som pode facilitar a remoção da placa ateromatosa, mas o efeito desse procedimento em vasos próximos ainda é matéria de estudos experimentais. MÉTODOS: Para determinar se a energia ultra-sônica compromete a produção de óxido nítrico, segmentos de artérias coronárias caninas foram expostos a baixos (0-10 W) e altos (25 W) níveis de energia por 15 segundos, utilizando-se protótipo de aparelho para a realização de endarterectomia. Após exposição, segmentos das artérias coronarianas foram estudados em organ chambers. Para os ensaios farmacológicos foram utilizadas as seguintes drogas:difosfato de adenosina (ADP), acetilcolina (Ach) e fluoreto de sódio (NaF) para a avaliação do relaxamento dependente do endotélio. O nitroprussiato de sódio (NPS) e o isoproterenol foram utilizados para a avaliação do relaxamento independente do endotélio. RESULTADOS: A aplicação de alta energia ultra-sônica comprometeu o relaxamento dependente do endotélio induzido por ADP (10-9 - 10-4 M), Ach (10-9 - 10-4 M) e NaF (0,5 -9,5 mM) em artérias coronarianas epicárdicas. Entretanto, baixos valores de energia ultra-sônica não alteraram o relaxamento dependente do endotélio (nem o relaxamento máximo e nem a EC50) induzido pelos mesmos agonistas. O relaxamento da musculatura lisa vascular induzido por isoproterenol (10-9 - 10-5 M) ou NPS (10-9 - 10-6 M) não foi comprometido, tanto por baixos, quanto por altos níveis de energia ultra-sônica. CONCLUSÃO: Os experimentos demonstram que altas energias ultra-sônicas alteram a função endotelial. Entretanto, o ultra-som não altera a habilidade de relaxamento da musculatura lisa vascular de artérias caninas epicárdicas.OBJECTIVE: Application of ultrasound energy by an endarterectomy probe can facilitate the removal of atheromatous plaque, but the effect of this procedure on surrounding vessel structure and function is still a matter of experimental investigations. METHODS: To determine whether ultrasound energy impairs the production of nitric oxide or damages vascular smooth muscle function, isolated canine epicardial coronary artery segments were exposed to either high (25 W) or low (0-10 W) ultrasonic energy outputs, for 15 seconds, using an endarterectomy device prototype. After exposure, segments of epicardial coronary artery were studied in organ chambers. The following drugs were used: adenosine diphosphate (ADP), acetylcholine (Ach) and sodium fluoride (NaF) to study endothelium-dependent relaxation and sodium nitroprusside (SNP) and isoproterenol to evaluate endothelium-independent relaxation. RESULTS: Application of high ultrasonic energy power impaired endothelium-dependent relaxation to ADP (10-9 - 10-4 M), Ach (10-9 - 10-4 M) and NaF (0.5 - 9.5 mM) in epicardial coronary arteries. However, low ultrasound energy output at the tip of the probe did not alter the endothelium-dependent relaxation (either maximal relaxation or EC50) to the same agonists. Vascular smooth muscle relaxation to isoproterenol (10-9 - 10-5 M) or SNP (10-9 - 10-6 M) was unaltered following exposure to either low or high ultrasonic energy outputs. CONCLUSION: These experiments currently prove that ultrasonic energy changes endothelial function of epicardial coronary arteries at high power. However, ultrasound does not alter the ability of vascular smooth muscle of canine epicardial coronary arteries to relax.Mayo FoundationCNP

Hippo-Independent Activation of YAP by the GNAQ Uveal Melanoma Oncogene through a Trio-Regulated Rho GTPase Signaling Circuitry

SummaryMutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Gαq family members, have been identified in ∼83% and ∼6% of uveal and skin melanomas, respectively. However, the molecular events underlying these GNAQ-driven malignancies are not yet defined, thus limiting the ability to develop cancer-targeted therapies. Here, we focused on the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway that controls organ size. We found that Gαq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase Cβ and the canonical Hippo pathway. Furthermore, we show that Gαq promotes the YAP-dependent growth of uveal melanoma cells, thereby identifying YAP as a suitable therapeutic target in uveal melanoma, a GNAQ/GNA11-initiated human malignancy

Lamb meat quality assessment by support vector machines

The correct assessment of meat quality (i.e., to fulfill the consumer's needs) is crucial element within the meat industry. Although there are several factors that affect the perception of taste, tenderness is considered the most important characteristic. In this paper, a Feature Selection procedure, based on a Sensitivity Analysis, is combined with a Support Vector Machine, in order to predict lamb meat tenderness. This real-world problem is defined in terms of two difficult regression tasks, by modeling objective (e.g. Warner-Bratzler Shear force) and subjective (e.g. human taste panel) measurements. In both cases, the proposed solution is competitive when compared with other neural (e.g. Multilayer Perceptron) and Multiple Regression approaches

The Acheulean site of As Gándaras de Budiño: synthesis and perspectives after 50 years of disencouters

El yacimiento paleolítico de As Gándaras de Budiño es un yacimiento clave en la Prehistoria antigua de la Península Ibérica. Aunque el yacimiento ha sido excavado en diferentes ocasiones, muchos de los aspectos geológicos y arqueológicos no son bien conocidos. Entre estos problemas está la cronología, que inicialmente fue atribuida al MIS 2 -originando una fuerte controversia-, aunque en la actualidad podemos afirmar que tiene una cronología del Pleistoceno Medio. Las industrias líticas son de tipo achelense de grandes lascas (LFA), con características similares a la de otros yacimientos de la Península Ibérica. Este artículo es un estado de la cuestión para el yacimiento, previo al reinicio de las investigaciones.As Gándaras de Budiño (GB) is a key locality for the Lower Palaeolithic record of the Iberian Peninsula. Although the site has been excavated in different occasions over the last decades, several geological and archaeological aspects are still not well known. Among other issues, the age of the lithic assemblage has been debated for a long time: despite an initial correlation to the MIS 2, new evidence rather points towards a Middle Pleistocene age instead. The lithic assemblage characterized as large flake acheulean type (LFA), with many similarities with other acheulean sites in the Iberian Peninsula. This work presents an updated overview of the current state of knowledge for GB while a new multidisciplinary research project has been recently initiatedinfo:eu-repo/semantics/publishedVersio

El yacimiento achelense de as Gándaras de Budiño: sín-tesis y perspectivas después de 50 años de desencuentros

ES: El yacimiento paleolítico de As Gándaras de Budiño es un yacimiento clave en la Prehistoria antigua de la Península Ibérica. Aunque el yacimiento ha sido excavado en diferentes ocasiones, muchos de los aspectos geológicos y arqueológicos no son bien conocidos. Entre estos problemas está la cronología, que inicialmente fue atribuida al MIS 2 -originando una fuerte controversia-, aunque en la actualidad podemos afirmar que tiene una cronología del Pleistoceno Medio. Las industrias líticas son de tipo achelense de grandes lascas (LFA), con características similares a la de otros yacimientos de la Península Ibérica. Este artículo es un estado de la cuestión para el yacimiento, previo al reinicio de las investigaciones.The Acheulean site of As Gándaras de Budiño: synthesis and perspectives after 50 years of disencoutersAs Gándaras de Budiño (GB) is a key locality for the Lower Palaeolithic record of the Iberian Peninsula. Although the site has been excavated in different occasions over the last decades, several geological and archaeological aspects are still not well known. Among other issues, the age of the lithic assemblage has been debated for a long time: despite an initial correlation to the MIS 2, new evidence rather points towards a Middle Pleistocene age instead. The lithic assemblage characterized as large flake acheulean type (LFA), with many similarities with other acheulean sites in the Iberian Peninsula. This work presents an updated overview of the current state of knowledge for GB while a new multidisciplinary research project has been recently initiate